In 1517, Charles moved from the Netherlands to Castile as the new King of Castile and Aragon. Germaine moved from Aragon to Castile to join his court as well, where the 17-year-old king took well to his 29-year-old stepgrandmother. He organized several tournaments and banquets in her honor. A year or thereabouts later, Germaine gave birth to a daughter, Isabel. It is widely speculated among historians that Charles was Isabel's father; Germaine refers to her in her will as the "Infanta Isabel"—a title that only makes sense if her father was the King.
Charles, Germaine, and Charles's sister Eleanor moved from Castile to Aragon in 1519, where he would be formally sworn in as King of Aragon. He would spend a year in Aragon, negotiating with its parliament and managing affairs. While in Barcelona, Charles arranged for Germaine to marry the margrave Johann of Brandenburg-Ansbach, a landless cadet and cousin of Joachim I, Elector of Brandenburg. Germaine left Spain to travel with Charles to Germany, where she was married.